Increased oxygen consumption rate observed in primary cultures of erythropoietin stimulated erythroid progenitor cells suggest a link between increased metabolism and erythropoietin stimulated erythropoiesis. In addition, erythropoietin stimulation increases glucose uptake in erythroid progenitor cells without change in fetal hemoglobin. Interestingly, mice (C57Bl6) on high fat diet treated with erythropoietin show the expected increase in hematocrit accompanied by a decrease in blood glucose level. This change in blood glucose is accompanied by an improvement in glucose tolerance and a decrease in cumulated fat mass. In addition to erythropoietin receptor expression in erythroid progenitor cells, erythropoietin receptor is also expressed in white adipose tissue. Deletion of the erythropoietin receptor in white adipose tissue does not alter the hematopoietic response in mice on high fat diet, although the decrease in cumulated fat mass is markedly reduced compared with control mice. These data suggest that the reduction of fat mass with erythropoietin treatment in mice is due in part to the erythropoietin stimulated increase of glucose uptake by erythroid progenitor cells and to erythropoietin response in non-hematopoietic tissue such as white fat.